The objective of the proposed research is to learn the detailed mechanism of action of certain metal activated kinases and related enzymes and to determine the specific role(s) which the metal ions play in catalysis. The enzymes to be studied, phosphoenolpyruvate carboxy-kinase and pyruvate kinase, require a divalent cation for activity and the paramagnetic cation Mn2 ion activates these enzymes. In the binary enzyme-Mn2 ion complex and in the ternary and higher enzyme-Mn2 ion complexes which contain substrate(s) a study of the effect of the enzyme bound Mn2 ion, on the relaxation rates of magnetic nuclei of the substrates (or inhibitors), the solvent, or the protein by nuclear magnetic resonance can yield kinetic, thermodynamic, and structural information about the environment of the cation. This information will give further details about the mechanism of action of these enzymes. When an enzyme such as pyruvate kinase of formyltetrahydrofolate synthetase requires a monovalent cation for activity and this requirement can be met by monomethylammonium ion which has a NMR signal, information about its environment and hence its function can be obtained. In these cases, where the enzymes have a divalent cation requirement (Mn2 ion) also, the monovalent probe can be used to obtain kinetic and thermodynamic information about the monovalent cation-enzyme interaction and the location of the monovalent cation with respect to the divalent cation in the various enzyme-metal complexes.